PY-60 is a thiazole-substituted derivative with 5-phenylisoxazole as its core structure, which can potently and specifically activate the transcriptional activity of YAP (EC50 = 1.6µM) [1]. PY-60 promotes the release of ANXA2 from the cell membrane, weakens its binding restriction to YAP, thereby enhancing the dephosphorylation of YAP and promoting its translocation into the nucleus, thereby activating the transcriptional coactivator function of YAP [1-2]. PY-60 is often used for tissue regeneration and repair [3].
In human retinoblastoma (RB) cells Y79 and RB3823, PY-60 (0, 1, 5, 10μM; 24h) treatment induced transcriptionally active YAP, thereby inhibiting the proliferation of RB cells Y79 and RB3823 [4]. In MDA-MB-231 cells, PY-60 (0, 2, 4, 8μM; 24h) promotes proliferation, migration, and invasion of high-density MDA-MB-231 cells [5]. In A549 and NCI-H358 cells, PY-60 (10μM; 24h) reversed the inhibitory effect of RFX2 overexpression on LUAD cells [6]. In HuCCT1 cells, PY-60 (10μM; 24h) reversed the inhibitory effects of PIN1 knockdown on cell migration, adhesion, and invasion [7].
In C57BL/6 WT mice, PY-60 (10mg/mL; smear; 10d) treatment enhances the colony forming potential of primary epidermal keratinocytes in mice [1]. In the rat subarachnoid hemorrhage model, PY-60 (0.2mg/kg; intraventricular administration; single injection) partially abolished the neuroprotective effect of NE-52-QQ57 [8].
References:
[1]. Shalhout SZ, Yang PY, Grzelak EM, et al. YAP-dependent proliferation by a small molecule targeting annexin A2. Nature Chemical Biology. 2021 Jul; 17(7): 767-775.
[2]. Martin JF. Regeneration and rejuvenation of skin by a topical YAP activator. Proceedings of the National Academy of Sciences. 2023 Aug 8; 120(32): e2309991120.
[3]. Grzelak EM, Elshan ND, Shao S, et al. Pharmacological YAP activation promotes regenerative repair of cutaneous wounds. Proceedings of the National Academy of Sciences. 2023 Jul 11; 120(28): e2305085120.
[4]. Zhong L, Meng X, Huang J, et al. Expression of yap suppresses cell proliferation and elevates the sensitivity of chemotherapy in retinoblastoma cells through lipid-peroxidation induced ferroptosis. Chinese Clinical Oncology. 2023 Oct 31; 12(5): 52.
[5]. Chen J, Su X, Tan Q, et al. Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications. Clinical and Translational Oncology. 2022 Nov; 24(11): 2136-2145.
[6]. Kong Z, Zhou P, Xu J, et al. RFX2 downregulates RASSF1 expression and YAP phosphorylation through Hippo signaling to promote immune escape in lung adenocarcinoma. Cell Division. 2025 Mar 11; 20(1): 7.
[7]. Wang Y, Liu Y, Chen H, et al. PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2. Cellular Oncology. 2024 Aug; 47(4): 1233-1252.
[8]. He Q, Zhou Y, Wu L, et al. Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage. Free Radical Biology and Medicine. 2024 Nov 20; 225: 333-345.
PY-60是一种以5-苯基异噁唑为核心结构的噻唑取代衍生物，能够强效且特异性地激活YAP的转录活性（EC50 = 1.6µM） [1]。PY-60促进ANXA2从细胞膜上释放，减弱其与YAP的结合限制，从而增强YAP的去磷酸化并促进其转位至细胞核内，进而激活YAP的转录共激活因子功能 [1-2]。PY-60常用于组织再生和修复 [3]。
在人类视网膜母细胞瘤（RB）细胞Y79和RB3823中，PY-60（0、1、5、10μM；24h）处理诱导转录活性YAP，从而抑制RB细胞Y79和RB3823的增殖 [4]。在MDA-MB-231细胞中，PY-60（0、2、4、8μM；24h）促进高密度MDA-MB-231细胞的增殖、迁移和侵袭 [5]。在A549和NCI-H358细胞中，PY-60（10μM；24h）可逆转RFX2过表达对LUAD细胞的抑制作用 [6]。在HuCCT1细胞中，PY-60（10μM；24h）可逆转PIN1敲低对细胞迁移、粘附和侵袭的抑制作用 [7]。
在C57BL/6野生型小鼠中，PY-60（10mg/mL；涂抹；10d）处理可增强小鼠原代表皮角质形成细胞的集落形成潜能 [1]。在大鼠蛛网膜下腔出血模型中，PY-60（0.2mg/kg；脑室内给药；单次注射）部分消除了NE-52-QQ57的神经保护作用 [8]。